EP2254569A1 - Protopanaxadiol-type ginsenoside compositions and uses thereof - Google Patents
Protopanaxadiol-type ginsenoside compositions and uses thereofInfo
- Publication number
- EP2254569A1 EP2254569A1 EP09704632A EP09704632A EP2254569A1 EP 2254569 A1 EP2254569 A1 EP 2254569A1 EP 09704632 A EP09704632 A EP 09704632A EP 09704632 A EP09704632 A EP 09704632A EP 2254569 A1 EP2254569 A1 EP 2254569A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- subject
- ginsenoside
- composition
- acetaldehyde
- disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 229930182494 ginsenoside Natural products 0.000 title claims abstract description 236
- 229940089161 ginsenoside Drugs 0.000 title claims abstract description 197
- 239000000203 mixture Substances 0.000 title claims abstract description 139
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims abstract description 156
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 117
- 235000019441 ethanol Nutrition 0.000 claims abstract description 87
- 238000000034 method Methods 0.000 claims abstract description 68
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 56
- 208000024891 symptom Diseases 0.000 claims abstract description 43
- PYXFVCFISTUSOO-HKUCOEKDSA-N (20S)-protopanaxadiol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@H]([C@@](C)(O)CCC=C(C)C)[C@H]4[C@H](O)C[C@@H]3[C@]21C PYXFVCFISTUSOO-HKUCOEKDSA-N 0.000 claims abstract description 41
- PYXFVCFISTUSOO-UHFFFAOYSA-N betulafolienetriol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC(C(C)(O)CCC=C(C)C)C4C(O)CC3C21C PYXFVCFISTUSOO-UHFFFAOYSA-N 0.000 claims abstract description 41
- SWQINCWATANGKN-UHFFFAOYSA-N protopanaxadiol Natural products CC(CCC=C(C)C)C1CCC2(C)C1C(O)CC1C3(C)CCC(O)C(C)(C)C3CCC21C SWQINCWATANGKN-UHFFFAOYSA-N 0.000 claims abstract description 41
- 208000035475 disorder Diseases 0.000 claims abstract description 30
- 201000010099 disease Diseases 0.000 claims abstract description 26
- 230000000694 effects Effects 0.000 claims description 65
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 claims description 38
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 claims description 38
- 239000002417 nutraceutical Substances 0.000 claims description 29
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 29
- 238000011010 flushing procedure Methods 0.000 claims description 22
- 230000001965 increasing effect Effects 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 230000015556 catabolic process Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 claims description 11
- 229960004245 silymarin Drugs 0.000 claims description 11
- 235000017700 silymarin Nutrition 0.000 claims description 11
- 230000002829 reductive effect Effects 0.000 claims description 10
- 206010019233 Headaches Diseases 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 208000002173 dizziness Diseases 0.000 claims description 7
- 231100000869 headache Toxicity 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 5
- 206010028813 Nausea Diseases 0.000 claims description 5
- 206010047700 Vomiting Diseases 0.000 claims description 5
- 230000008693 nausea Effects 0.000 claims description 5
- 230000008673 vomiting Effects 0.000 claims description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 239000005022 packaging material Substances 0.000 claims description 4
- 239000000779 smoke Substances 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 208000001953 Hypotension Diseases 0.000 claims description 3
- 206010033557 Palpitations Diseases 0.000 claims description 3
- 206010000059 abdominal discomfort Diseases 0.000 claims description 3
- 230000037396 body weight Effects 0.000 claims description 3
- 230000036543 hypotension Effects 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 206010017856 Gastritis alcoholic Diseases 0.000 claims description 2
- 206010019133 Hangover Diseases 0.000 claims description 2
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 2
- 206010067125 Liver injury Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 235000017276 Salvia Nutrition 0.000 claims description 2
- 240000007164 Salvia officinalis Species 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 201000005988 alcoholic gastritis Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 235000019504 cigarettes Nutrition 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 230000001079 digestive effect Effects 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 210000003128 head Anatomy 0.000 claims description 2
- 231100000234 hepatic damage Toxicity 0.000 claims description 2
- 210000003026 hypopharynx Anatomy 0.000 claims description 2
- 201000006866 hypopharynx cancer Diseases 0.000 claims description 2
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 2
- 210000000867 larynx Anatomy 0.000 claims description 2
- 201000004962 larynx cancer Diseases 0.000 claims description 2
- 201000010901 lateral sclerosis Diseases 0.000 claims description 2
- 230000008818 liver damage Effects 0.000 claims description 2
- 208000026037 malignant tumor of neck Diseases 0.000 claims description 2
- 230000004060 metabolic process Effects 0.000 claims description 2
- 208000005264 motor neuron disease Diseases 0.000 claims description 2
- 210000003300 oropharynx Anatomy 0.000 claims description 2
- 201000006958 oropharynx cancer Diseases 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 description 56
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 26
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 26
- 239000002552 dosage form Substances 0.000 description 26
- 230000035622 drinking Effects 0.000 description 26
- 239000002775 capsule Substances 0.000 description 20
- 235000015872 dietary supplement Nutrition 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- -1 ginsenoside RbI Natural products 0.000 description 14
- 235000013361 beverage Nutrition 0.000 description 12
- 240000004371 Panax ginseng Species 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 229920002472 Starch Polymers 0.000 description 10
- 235000008434 ginseng Nutrition 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 9
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 9
- 239000008101 lactose Substances 0.000 description 9
- SHCBCKBYTHZQGZ-DLHMIPLTSA-N protopanaxatriol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2[C@@H](O)C[C@@]3(C)[C@]4(C)CC[C@H]([C@](C)(O)CCC=C(C)C)[C@H]4[C@H](O)C[C@@H]3[C@]21C SHCBCKBYTHZQGZ-DLHMIPLTSA-N 0.000 description 9
- BBEUDPAEKGPXDG-UHFFFAOYSA-N protopanaxatriol Natural products CC(CCC=C(C)C)C1CCC2(C)C1C(O)CC3C4(C)CCC(O)C(C)(C)C4C(O)CC23C BBEUDPAEKGPXDG-UHFFFAOYSA-N 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- 206010016825 Flushing Diseases 0.000 description 8
- 235000003140 Panax quinquefolius Nutrition 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000000454 talc Substances 0.000 description 8
- 229910052623 talc Inorganic materials 0.000 description 8
- 239000007903 gelatin capsule Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241000208343 Panax Species 0.000 description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 230000001815 facial effect Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000002483 medication Methods 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000001010 compromised effect Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 230000037406 food intake Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 235000002789 Panax ginseng Nutrition 0.000 description 4
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 235000020097 white wine Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 235000002791 Panax Nutrition 0.000 description 3
- 208000001871 Tachycardia Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 229960001948 caffeine Drugs 0.000 description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 235000020710 ginseng extract Nutrition 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 3
- 229960003908 pseudoephedrine Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 235000021055 solid food Nutrition 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000006794 tachycardia Effects 0.000 description 3
- FMIMFCRXYXVFTA-FUAOEXFOSA-N (4as,6ar,6as,6br,8ar,12ar,14bs)-2,2,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1h-picene-4a-carboxylic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C FMIMFCRXYXVFTA-FUAOEXFOSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 206010001598 Alcohol intolerance Diseases 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 241000282994 Cervidae Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 108010000817 Leuprolide Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 240000005373 Panax quinquefolius Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 241000282458 Ursus sp. Species 0.000 description 2
- 201000007930 alcohol dependence Diseases 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 230000002528 anti-freeze Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000021472 generally recognized as safe Nutrition 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- RGLRXNKKBLIBQS-XNHQSDQCSA-N leuprolide acetate Chemical compound CC(O)=O.CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 RGLRXNKKBLIBQS-XNHQSDQCSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 235000017709 saponins Nutrition 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 150000004072 triols Chemical class 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- XMQUEQJCYRFIQS-YFKPBYRVSA-N (2s)-2-amino-5-ethoxy-5-oxopentanoic acid Chemical compound CCOC(=O)CC[C@H](N)C(O)=O XMQUEQJCYRFIQS-YFKPBYRVSA-N 0.000 description 1
- VCNKUCWWHVTTBY-UHFFFAOYSA-N 18alpha-Oleanane Natural products C1CCC(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C)(C)CC5C4CCC3C21C VCNKUCWWHVTTBY-UHFFFAOYSA-N 0.000 description 1
- ZUXNULGHCOXCFL-UHFFFAOYSA-N 2-(4-tert-butyl-2,6-dimethylphenyl)acetonitrile Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC#N ZUXNULGHCOXCFL-UHFFFAOYSA-N 0.000 description 1
- FMIMFCRXYXVFTA-UHFFFAOYSA-N 3-Oxo-12-oleanen-28-oic acid Natural products C1CC(=O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C FMIMFCRXYXVFTA-UHFFFAOYSA-N 0.000 description 1
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 1
- 101150038502 ALDH2 gene Proteins 0.000 description 1
- 241000380131 Ammophila arenaria Species 0.000 description 1
- 108010053481 Antifreeze Proteins Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 240000008415 Lactuca sativa Species 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 241000428198 Lutrinae Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000283216 Phocidae Species 0.000 description 1
- 229920005830 Polyurethane Foam Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000320380 Silybum Species 0.000 description 1
- 235000010841 Silybum marianum Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 235000006468 Thea sinensis Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 235000020279 black tea Nutrition 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000008162 cooking oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 235000021185 dessert Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- FFDHYUFECJTEAY-UHFFFAOYSA-N epimacherinic acid Natural products CC1(C)CCC2(CCC3(C)C(CCC4C5(C)CCCC(C)(C)C5CCC34C)C2C1)C(=O)O FFDHYUFECJTEAY-UHFFFAOYSA-N 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000020375 flavoured syrup Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 239000002316 fumigant Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- SIOMFBXUIJKTMF-UHFFFAOYSA-N hypoglauterpenic acid Natural products C1CC(O)C(C)(C)C2=CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C SIOMFBXUIJKTMF-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229940087857 lupron Drugs 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003264 margarine Substances 0.000 description 1
- 235000013310 margarine Nutrition 0.000 description 1
- 235000010746 mayonnaise Nutrition 0.000 description 1
- 239000008268 mayonnaise Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- BPAWXSVOAOLSRP-UHFFFAOYSA-N oleanane Natural products CCCCCCCCCCCCCCCC(=O)OC1CCC2(C)C(CCC3(C)C2CC=C4C5CC(C)(C)CCC5(C)C(O)CC34C)C1(C)C BPAWXSVOAOLSRP-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 235000021400 peanut butter Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008063 pharmaceutical solvent Substances 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011496 polyurethane foam Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000012045 salad Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
- 235000020125 yoghurt-based beverage Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Definitions
- composition does not include the natural source of the component, but can, in certain embodiments, encompass a physically or chemically modified or processed form of the natural source, such as an extract of the natural source.
- effective amount refers to the amount of ginsenoside composition that is sufficient to produce a desirable or beneficial effect when contacted for example to an aldehyde dehydrogenase enzyme, or, as another example, when administered to a subject.
- the "effective amount" of a ginsenoside composition is, e.g., the amount to increase the rate that acetaldehyde concentration is reduced in a subject compared to the rate that acetaldehyde concentration is reduced in the absence of the ginsenoside composition. In some embodiments, the "effective amount” is, e.g., the amount to prevent or ameliorate a symptom of elevated acetaldehyde concentration in a subject, or to reduce the likelihood or risk in a subject for a disease or disorder caused by acetaldehyde exposure.
- symptom refers to a physical condition which indicates a particular illness or disorder (e.g., Longman Dictionary of Contemporary English (1995). Third edition) detectable by the subject suffering from a particular disease or disorder or detectable by a person other than the subject without verbal information from said subject.
- symptom refers to a physical condition which indicates a particular illness or disorder (e.g., Longman Dictionary of Contemporary English (1995). Third edition) detectable by the subject suffering from a particular disease or disorder or detectable by a person other than the subject without verbal information from said subject.
- ginsenosides While intending to be bound by any particular theory or limitation, it is believed that protopanaxadiol type of ginsenosides, but generally not, for example, protopanaxatriol ginsenosides, increase the activity of aldehyde dehydrogenase (ALDH). As such, without intending to be bound by any particular theory or limitation, the ginsenoside compositions provided herein are believed to increase the rate that aldehyde levels would be otherwise reduced in vivo.
- ADH aldehyde dehydrogenase
- the ratio of protopanaxadiol type of ginsenoside to protopanaxadiol type is about 90:10, about 80:20 or about 60:40.
- the ginsenoside composition consists of a non- ginsenoside fraction and a ginsenoside fraction, wherein the ginsenoside fraction comprises at least 10, 15, 20, 25, 30, 50, 75 or 95 %(w/w) of a protopanaxadiol type of ginsenoside, for instance, one or more of RbI, Rb2, Rc and Rd.
- ginsenosides including protopanaxadiol type of ginsenosides such as ginsenosides RbI, Rb2, Rc and Rd, are known to those of skill in the art ⁇ see, e.g., Yu et al., Chem. Pharm. Bull. 2007, 55(2), 231-235; Court, "The Principal Active Chemicals in Panax species” in Ginseng: The Genus Panax (Court, ed., Harwood Academic Publishers, Amsterdam, The Netherlands, 2000), both of which are incorporated herein by reference in their entireties).
- Protopanaxadiol type ginsenosides can be obtained by any method known in the art including, for example, by purification from natural plant sources, for example, ginseng including Panax ginseng (Asian or Korean ginseng) and Panax quinquefolius (American ginseng), and cultured plant sources including ginseng cultures ⁇ see, e.g., Ginseng: The Genus Panax (Court, ed., Harwood Academic Publishers, Amsterdam, The Netherlands, 2000) and citations cited therein; Yua et al., Biochemical Engineering Journal 2002, 11, 21 1-215, each of which is incorporated herein by reference).
- a composition as provided herein can be in the form of a dietary supplement or nutraceutical.
- a dietary supplement or nutraceutical comprising or consisting essentially of a protopanaxadiol type of ginsenoside.
- the dietary supplement or nutraceutical comprises or consists essentially of one or more of ginsenoside RbI, Rb2, Rb3, Rc, Rd, Rg3, Rh2, RsI and/or Rs2.
- the dietary supplement or nutraceutical comprises or consists essentially of one or more of ginsenoside RbI, Rb2, Rc and/or Rd.
- the composition of the invention typically comprises one or more consumable fillers or carriers.
- consumable means the filler or carrier that is generally suitable for, or is approved by a regulatory agency of the Federal or a state government, for consumption by animals, and more particularly by humans.
- dietary supplement or “nutraceutical” is the meaning of those terms as defined by a regulatory agency of the Federal or a state government, including the United States Food and Drug Administration.
- the dietary supplement or nutraceutical can be used to reduce the risk in a subject for a disease or disorder caused by intake of ethyl alcohol comprising administering to a subject in need thereof an amount of the ginsenoside in the dietary supplement or nutraceutical effective to increase catabolism of acetaldehyde in the subject, wherein acetaldehyde is a product of ethyl alcohol consumption by the subject and wherein increasing catabolism of acetaldehyde reduces a risk for a disease or disorder in the subject caused by intake of the ethyl alcohol.
- a dietary supplement or nutraceutical as provided herein is intended to be orally taken or consumed.
- the dietary supplement or nutraceutical can be in a solid form or a liquid form.
- compositions of the invention can be a beverage, such as but not limited to fortified mineral water, fortified distilled water, a fruit juice-based beverage, a shake, a milk-based beverage, a dairy product-based beverage, a yoghurt-based beverage, a carbonated water-based beverage, an alcoholic drink, a coffee- based beverage, a green tea-based beverage, a black tea-based beverage, a grain-based beverage, a soybean-based beverage, or a beverage based on plant extracts.
- the compositions of the present invention may be combined with other foodstuff, for example, syrups, starches, grains, or grain flour.
- the ginsenoside composition provided herein is suitable for oral administration to a subject.
- the ginsenoside composition provided herein is a nutraceutical composition and further comprises a physiologically acceptable carrier, excipient, diluent or solvent.
- compositions wherein the ginsenoside composition, as described above, is a pharmaceutical composition and further comprises a pharmaceutical acceptable carrier, excipient, diluent or solvent.
- Pharmaceutical carriers, excipients, diluents or solvents can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like.
- Suitable excipients are well-known to those skilled in the art of pharmacy, and non-limiting examples of suitable excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. Whether a particular excipient is suitable for incorporation into a pharmaceutical composition depends on a variety of factors well known in the art including, but not limited to, the way in which the dosage form will be administered to a patient and the specific active ingredients in the dosage form.
- the pharmaceutical composition if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents.
- a pharmaceutical composition is formulated to be compatible with its intended route of administration.
- routes of administration include, but are not limited to, parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), intranasal, and transdermal (topical) administration.
- the composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous, subcutaneous, intramuscular, oral, intranasal or topical administration to subjects.
- a pharmaceutical composition is formulated in accordance with routine procedures for oral administration to humans.
- compositions for intravenous administration are solutions in sterile isotonic aqueous buffer.
- the ingredients of pharmaceutical compositions as provided herein are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent.
- a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent.
- the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline.
- an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.
- the unit dosage form is a container, preferably a sterile container, containing an effective amount of ginsenoside composition and a pharmaceutically acceptable carrier or excipient.
- an article of manufacture is provided that can simplify the administration of ginsenoside compositions to a subject.
- a typical article of manufacture of the invention comprises a unit dosage form of ginsenoside compositions.
- the article of manufacture includes instruction means indicating or suggesting a dosing regimen including, but not limited to, actual doses, monitoring procedures, and other monitoring information.
- the packaging material and container included in the article of manufacture are designed to protect the stability of the product during storage and shipment.
- Article of manufacture of the invention can further comprise devices that are useful for administering the unit dosage forms.
- devices include, but are not limited to, syringes, drip bags, patches, and inhalers.
- compositions as provided herein can, for example, be suitable for oral administration, and orally consumable compositions including but not limited to dietary supplements or nutraceutical compositions of the invention, can be presented as discrete dosage forms, such as, but are not limited to, tablets (e.g., chewable tablets), caplets, capsules, and liquids (e.g., flavored syrups).
- dosage forms contain predetermined amounts of active ingredients, and may be prepared by methods of pharmacy well known to those skilled in the art. See generally, Remington: Science and Practice of Pharmacy, 21 st ed., Lippincott Williams & Wilkins, Philadelphia PA (2005); Ansel's Pharmaceutical Dosage
- compositions as provided herein can comprise one or more protopanaxadiol-type ginsenoside in combination with one or more active agents.
- active agents can include, for example, a vitamin, an anti-oxidant, an anti-inflammatory agent, a non-steroid anti-inflammatory agent, an anti-histamine and the like.
- a combination composition comprises one or more protopanaxadiol-type ginsenoside in combination with glutamine or silymarin (flavonoid complex of Slybum marianum or milk thistle).
- a combination composition comprises one or more protopanaxadiol-type ginsenoside in combination with aspirin or ibuprofen.
- combination compositions comprising a protopanaxadiol-type ginsenoside and glutamine or silymarin or both glutamine and silymarin, can be in a unit dosage form.
- a combination composition in unit dosage form can comprise about 5 mg to about 500 mg protopanaxadiol type ginsenoside, about 50 mg to about 3 g glutamine and/or about 20 mg to about 800 mg silymarin.
- Such unit dosage forms optionally can further comprise one or more diluent, carrier, vehicle, stabilizer, flavoring, or other component known to those of skill in the art for inclusion into unit dosage forms when preparing, for instance, nutraceutical or pharmaceutical compositions.
- ginsenoside including the ginsenoside compositions as described above.
- the methods provided comprise administering a ginsenoside to a subject.
- the ginsenoside can be any ginsenoside, or combination of ginsenosides, known in the art.
- the ginsenoside can one or more of a protopanaxadiol type, protopanaxatriol type, oleanane type and/or other types, as described, for instance, in Court, "The Principal Active Chemicals in Panax species" in Ginseng: The Genus Panax (Court, ed., Harwood Academic Publishers, Amsterdam, The Netherlands, 2000), incorporated herein by reference in its entirety.
- methods for the increased reduction of an aldehyde concentration in a subject comprising administering to a subject in need thereof an amount of a ginsenoside effective to increase reduction the aldehyde concentration in the subject relative to a condition where the subject is not administered the ginsenoside.
- the aldehyde is acetaldehyde.
- methods for reducing an aldehyde concentration in a subject comprising administering to a subject in need thereof an amount of a ginsenoside effective to reduce the aldehyde concentration in the subject.
- a ginsenoside effective to reduce the aldehyde concentration in the subject.
- phrases used herein in conjunction with the methods provided for use of a ginsenoside such as "reduce an aldehyde concentration in a subject” and the like, can, for instance, mean increasing the rate at which an aldehyde is reduced in a subject.
- protopanaxadiol type of ginsenosides decrease activity of alcohol dehydrogenases.
- phrases used herein in conjunction with the methods provided for use of a ginsenoside such as "reduce an aldehyde concentration in a subject” and similar phrases, can, for instance, mean prevent or reduce an aldehyde concentration in a subject that would otherwise occur in the absence of the ginsenoside being administered to the subject. It will also be understood, that without intent to be limited to any particular theory or limitation, that protopanaxadiol type of ginsenosides administered to a subject may both decrease alcohol dehydrogenase activities and increase aldehyde dehydrogenase activities in the subject.
- methods are provided for preventing or ameliorating a symptom of elevated acetaldehyde concentration in a subject comprising administering to a subject in need thereof an amount of a ginsenoside effective to prevent or ameliorate a symptom of elevated acetaldehyde concentration in the subject.
- methods for reducing a likelihood or risk in a subject for a disease or disorder caused by intake of ethyl alcohol comprising administering to a subject in need thereof an amount of a ginsenoside effective to increase catabolism of acetaldehyde in the subject.
- the acetaldehyde can, for example, be a product of ethyl alcohol consumption by the subject wherein increasing catabolism of acetaldehyde reduces the likelihood or risk for a disease or disorder caused by the subject's intake of the ethyl alcohol.
- the subject is human.
- the subject has an altered ethyl alcohol metabolism.
- the subject has a reduced aldehyde dehydrogenase subtype 2 (ALDH2) activity.
- the subject is a homozygous or heterozygous carrier of the ALDH2*2 allele, as discussed above.
- methods are provided for increasing the catabolism of acetaldehyde in a subject, thereby reducing acetaldehyde concentrations in the subject.
- methods can, for example, be utilized for alleviating discomfort of the acute symptoms of acetaldehyde (such as, for example, dizziness, tachycardia, flushing, headache, and so forth).
- Acetaldehyde exposure can, for example, arise as a result of ethyl alcohol consumption.
- acetaldehyde is a product of such as, but not limited to, cigarette smoke or exposure to acetaldehyde in the environment outside of the subject.
- a symptom of elevated acetaldehyde concentration comprises flushing, elevated heart rate, palpitations, hypotension, nausea, dizziness, headache, vomiting, diarrhea, upset stomach, ataxia or confused consciousness.
- the disease or disorder comprises hangover, alcoholic gastritis or alcohol-induced liver damage.
- the disease or disorder comprises upper aerodigestive tract cancers, digestive tract cancers or breast cancer.
- the upper aerodigestive tract cancer comprises esophageal, oropharynx, hypopharynx, larynx, head or neck cancer.
- the digestive cancer comprises stomach or colon cancer.
- the disease or disorder comprises late-onset
- Alzheimer's disease hypertension, myocardial infarction, Parkinson's disease, amyotropic lateral sclerosis, and cerebral ischemia.
- the acetaldehyde concentration is in the blood, salvia and/or tissue of the subject.
- the methods provided herein prevent or ameliorate a symptom of elevated aldehyde concentration in a subject, wherein said aldehyde is a substrate of ALDH2, comprising administering to a subject in need thereof an amount of a ginsenoside effective to prevent or ameliorate a symptom of elevated aldehyde concentration in the subject.
- methods for increasing the activity of ALDH2 in a subject comprising administering an amount of ginsenoside effective to increase the activity of ALDH2 in the subject are provided.
- a method can comprise administering to a subject an amount of ginsenoside effective to decrease the activity of an alcohol dehydrogenase in the subject.
- methods comprising administering to a subject an amount of ginsenoside effective to increase an ALDH activity and decrease an alcohol dehydrogenase activity.
- Toxicity associated from drinking alcohols including those in antifreeze can be lethal even fatal to animals.
- methods comprising administering a ginsenoside to an animal in an amount effect to increase ALDH activities in the animal, decrease alcohol dehydrogenase activities in the animal, or both increase ALDH activity and decrease alcohol dehydrogenase activities in the animal.
- Such methods can, for example, alleviate a symptom of an alcohol in an animal.
- Alcohols can include methanol, ethyl alcohol, ethylene glycol, butanol, isopropyl alcohol, and the like.
- the methods provided increase the rate of reducing an aldehyde in an animal.
- the methods prevent or to reduce the catalysis of an alcohol to aldehyde in an animal.
- the animal is a mammal.
- the animal is a companion, domesticated, research or farm animal (e.g., dogs, rabbits, rats, mice, guinea pigs, cats, pigs, sheep, goats, horses, cattle and the like) or wild animal (e.g, monkeys, bears, deer, seals, otters and so forth).
- the amount of ginsenoside administered in the methods provided above that will be effective, for example, for the increased reduction of aldehyde concentration, prevention or amelioration of a symptom of elevated aldehyde concentration, or reducing a likelihood or risk for a disease or disorder caused by intake of an alcohol, in the subject will vary with the nature and severity of the exposure to the aldehyde and the route by which the ginsenoside is administered. Frequency and dosage will also vary according to factors specific for each subject or patient such as age, weight, response, and the past medical history of the patient. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.
- Suitable regiments can be selected by one skilled in the art by considering such factors and by following, for example, dosages reported in the literature and recommended in the Physician 's Desk Reference (57th ed., 2003).
- Exemplary doses of ginsenoside in the methods provided herein include milligram or microgram amounts of total ginsenoside per kilogram of subject weight (e.g., about 1 microgram per kilogram to about 100 milligrams per kilogram, about 100 micrograms per kilogram to about 5 milligrams per kilogram, or about 1 microgram per kilogram to about 50 micrograms per kilogram).
- the daily dose range of a ginsenoside described herein lie with the range of from about 0.01 mg of total ginsenoside to about 1000 mg per day.
- the daily dose is administered twice daily in equally divided doses. More typically, doses of the ginsenoside will be administered prior to an expected exposure to an aldehyde, or after exposure to the aldehyde is apparent, for example, by manifestation of the acute symptoms of aldehyde exposure in the subject.
- a daily dose range should be from about 5 mg to about 500 mg per day, more specifically, between about 10 mg and about 200 mg per day.
- the therapy should be initiated at a lower dose, perhaps about 1 mg to about 25 mg, and increased if necessary up to about 200 mg to about 1000 mg per day as either a single dose or divided doses, depending on the subject's global response. It may be necessary to use dosages of the active ingredient outside the ranges disclosed herein in some cases, as will be apparent to those of ordinary skill in the art.
- the dietitian, clinician or treating physician wall know how and when to interrupt, adjust, or terminate therapy in conjunction with individual patient responses and conditions, as will be readily known by those of ordinary skill in the art.
- the amount of total ginsenoside administered to a subject in a method as provided herein is about 5 ⁇ g/kg, about 50 ⁇ g/kg, about 100 ⁇ g/kg, about 150 ⁇ g/kg, about 250 ⁇ g/kg, about 500 ⁇ g/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg/kg, about 25 mg/kg, about 50 mg/kg, about 75 mg/kg, about 100 mg/kg or more.
- the dosage of total ginsenoside administered is about 0.01 mg to about 10 mg, about 0.1 mg to about 30 mg, about 0.5 mg to about 50 mg, about 1.0 mg to about 60 mg, about 5.0 mg to about 80 mg, or about 10 mg to about 100 mg, per kilogram of the subject's body weight per day.
- the ginsenoside will be administered to the subject about 10 min, about 20 min, about 40 min, about 1 h, about 2 h, about 3 h, about 1O h, about
- the ginsenoside will be administered to the subject at the same time when the event causing elevated aldehyde concentration, such as, for example, ethyl alcohol consumption, occurs.
- the ginsenoside will be administered to the subject about 10 min, about 20 min, about 40 min, about 1 h, about 2 h, about 3 h, about 6 h or about
- the administration schedule of the ginsenoside comprises single or repeated administration according to the needs of the subject as determined by the skilled artisan.
- a combination of ginsenoside and glutamine are administered to a subject.
- Amounts of glutamine to be administered to the subject typically range, for example, from about 50 milligrams to about 3 grams, from about 150 milligrams to about 1.5 grams, from about 400 milligrams to about 2 grams, more typically about
- a combination of ginsenoside and silymarin are administered to a subject, typically about 20 milligrams to about 800 milligrams, more typically about 100 milligrams to about 600 milligrams or about 400 grams of silymarin are administered to the subject per day.
- the subject experiencing an elevated acetaldehyde level has been exposed to acetaldehyde from environmental sources, such as a wood burning fire, tobacco smoke, automobile or diesel exhaust.
- the subject experiencing an elevated acetaldehyde level is a carrier of a compromised aldehyde dehydrogenase.
- the subject experiencing an elevated acetaldehyde level has been consuming ethyl alcohol.
- Alcohol Dehydrogenase (ADH) Activity demonstrates that some but not all ginsenosides decrease the catalytic activity of alcohol dehydrogenase (ADH).
- ADH alcohol dehydrogenase
- protopanaxadiol type ginsenosides were found to decrease ADH activity whereas protopanaxatriol type ginsenosides had no significant effect on ADH activity.
- Ginsenosides RbI, Rb2, Rc, Rd, Re and RgI were obtained from ChromaDex
- ginsenosides were dissolved in DMSO to prepare a stock solution. Prior to performing an activity assay, portions of a ginsenosides stock solution were diluted in aqueous reaction buffer solution and from which samples were taken and assayed for activity.
- ADH activity was measured in a colorimetric assay as described in Gibla and
- FIG. 1 provides a comparison of the averaged effects of protopanaxadiols RbI, Rb2, Rc and Rd versus the averaged effects of protopanaxatriols Re and RgI .
- Figure 2 provides a comparison of the averaged effects of protopanaxadiols RbI, Rb2, Rc and Rd versus the averaged effects of protopanaxatriols Re and RgI .
- concentrations greater than about 50 ⁇ g/mL of a protopanaxadiol type of ginsenoside reduce the activity of ADH.
- ginsenosides RbI, Rb2, Rc and Rd reduced ADH activity and the protopanaxatriol type ginsenosides Re and RgI did not have a significant effect on ADH activity (Figure 1).
- the average decrease in ADH activity by protopanaxadiols as compared to protopanaxatriols was >20% ( Figure 2). 8.2. Al
- This example demonstrates that some but not all ginsenosides increase the catalytic activity of ALDH.
- protopanaxadiol type ginsenosides were found to increase ALDH activity whereas protopanaxatriol type ginsenosides had no significant effect on ALDH activity.
- FIG. 4 provides a comparison of the averaged effects of protopanaxadiols RbI, Rb2, Rc and Rd versus the averaged effects of protopanaxatriols Re and RgI .
- concentrations greater than about 5 ⁇ g/mL of a protopanaxadiol type ginsenoside increases the activity of ALDH.
- ginsenosides RbI, Rb2, Rc and Rd increased ALDH activity and protopanaxatriol ginsenosides Re and RgI did not have a significant effect on ALDH activity (Figure 3).
- the average increase in ALDH activity by protopanaxadiols as compared to protopanaxatriols was >50% ( Figure 4).
- This example describes the preparation of different ginsensoside nutraceutical compositions.
- Ginsenoside composition A ginseng extract having a 30% total ginsenoside fraction was prepared in powdered form and encapsulated (25 mg extract per capsule). The ratio of the protopanaxadiol to protopanaxatriol type of ginsenosides in the ginsenoside fraction was about 60:40. The ginsenoside composition preparation used in this study is considered to be generally recognized as safe (GRAS).
- a) The subject records his or her pulse at rest while sitting before drinking any alcohol.
- the subject should not take any caffeine, pseudoephedrine, blood pressure medications, or any other medications known to alter heart rate for at least 24 hours, and no solid foods for at least 4 hours, prior to anticipated alcohol intake time.
- the subject should have a family member or friend judge "redness," and take a facial photograph of the subject for pre-drinking baseline. The subject should also evaluate his or her own facial flushing.
- b) Take 2 capsules of the ginsenoside composition.
- a ginsenoside composition as provided herein can reduce symptoms, such as, for example, discomfort, flushing, and increased heart rate associated with alcohol sensitivity.
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2331008P | 2008-01-24 | 2008-01-24 | |
PCT/US2009/000431 WO2009094177A1 (en) | 2008-01-24 | 2009-01-23 | Protopanaxadiol-type ginsenoside compositions and uses thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2254569A1 true EP2254569A1 (en) | 2010-12-01 |
EP2254569B1 EP2254569B1 (en) | 2012-11-28 |
Family
ID=40578016
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP09704632A Not-in-force EP2254569B1 (en) | 2008-01-24 | 2009-01-23 | Protopanaxadiol-type ginsenoside compositions and uses thereof |
Country Status (14)
Country | Link |
---|---|
US (1) | US8440632B2 (en) |
EP (1) | EP2254569B1 (en) |
JP (1) | JP5523348B2 (en) |
KR (2) | KR101648987B1 (en) |
CN (1) | CN101977600B (en) |
AU (1) | AU2009206753B2 (en) |
CA (1) | CA2713104C (en) |
DK (1) | DK2254569T3 (en) |
ES (1) | ES2400491T3 (en) |
HK (1) | HK1144772A1 (en) |
MY (1) | MY160074A (en) |
NZ (1) | NZ587134A (en) |
TW (1) | TWI440463B (en) |
WO (1) | WO2009094177A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017532053A (en) * | 2014-10-28 | 2017-11-02 | ロブスト シード テクノロジー エーアンドエフ アクチエボラーグ | Improved method of seed priming |
CN109758464A (en) * | 2019-03-21 | 2019-05-17 | 淮阴师范学院 | Application of Vietnam ginsenoside R4 in preparation neurodegenerative disease therapeutic agent |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5563285B2 (en) * | 2009-12-14 | 2014-07-30 | ライオン株式会社 | Food / beverage product, pharmaceutical product, or quasi-drug, method for stabilizing protopanaxatriol, and method for stabilizing protopanaxadiol |
US20150087702A1 (en) * | 2011-11-22 | 2015-03-26 | The Johns Hopkins University | Methods and compositions for reducing alcohol toxicity |
KR101446743B1 (en) * | 2012-06-11 | 2014-10-01 | 한국생명공학연구원 | Composition for preventing and treating alcoholic gastric ulcer comprising Silymarin |
CN102727508B (en) * | 2012-07-15 | 2014-09-24 | 浙江大学 | Preparation of panaxadiol saponins component and pharmaceutical application for prevention and treatment of Parkinson disease |
US11338120B2 (en) | 2012-08-29 | 2022-05-24 | Palo Alto Investors LP | Methods and devices for treating parasympathetic bias mediated conditions |
WO2014178803A1 (en) * | 2013-04-29 | 2014-11-06 | Alkoçlar Erdal Can | A composition for use in the treatment of alcohol addiction |
KR101621356B1 (en) * | 2014-09-05 | 2016-05-17 | 한국과학기술원 | Use of ginsenoside F2 for prophylaxis and treatment of liver disease |
CN115887456A (en) | 2015-03-26 | 2023-04-04 | 杰奎琳·M·艾弗森 | Methods and compositions for inhibiting symptoms associated with hangover |
KR101641477B1 (en) * | 2016-01-19 | 2016-07-20 | 이국진 | Cultivation method coffee tree by red ginseng extract |
CN106619669B (en) * | 2016-12-02 | 2019-03-29 | 延边大学 | Application of the protopanoxadiol saponin(e in the drug of preparation prevention and treatment inflammation disease |
CN106511360A (en) * | 2016-12-02 | 2017-03-22 | 上海芮范生物科技有限公司 | Composition containing ginsenoside Rg3 and silymarin and medicine |
CN112274524A (en) * | 2017-08-24 | 2021-01-29 | 浙江大学 | Application of panaxadiol saponin Rb component in preparing medicine for preventing and treating metabolic disorder related diseases |
KR102053208B1 (en) * | 2018-03-15 | 2019-12-06 | 숙명여자대학교 산학협력단 | Compositions for muscle regeneration containing Ginsenoside Rb1 and Rb2 as active ingedients |
US11000537B2 (en) * | 2018-10-17 | 2021-05-11 | Amorepacific Corporation | Composition comprising novel ginsenoside |
US11000538B2 (en) * | 2018-10-31 | 2021-05-11 | Amorepacific Corporation | Composition for enhancing exercise ability or anti-fatigue comprising novel ginsenoside |
US20230270711A1 (en) | 2019-10-10 | 2023-08-31 | Zobrius Pharma As | Improved Anti-Hangover Composition, Its Preparation and Uses |
KR102654669B1 (en) * | 2021-06-30 | 2024-04-04 | 경희대학교 산학협력단 | Silydianin loaded mountain ginseng root mediated gold nanoemulsion and use thereof |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1574806A (en) * | 1976-06-03 | 1980-09-10 | Inverni Della Beffa Spa | Production of purified ginseng extracts and pharmaceutical compositions containing the extracts |
US4966893A (en) | 1989-01-13 | 1990-10-30 | Pang Peter K T | Method for treatment of senile dementia |
JPH04316448A (en) | 1991-04-12 | 1992-11-06 | Iwatani Internatl Corp | Production of carrot fine powder |
US5547671A (en) * | 1995-09-20 | 1996-08-20 | Duthinh; Phu | Anti-intoxication composition |
JP3656972B2 (en) * | 1997-02-14 | 2005-06-08 | 丸善製薬株式会社 | Alcohol smell reducing agent |
US6083932A (en) | 1997-04-18 | 2000-07-04 | Cv Technologies Inc. | Pharmaceutical compositions derived from ginseng and methods of treatment using same |
CA2301860C (en) | 1997-08-28 | 2009-05-26 | Cv Technologies Inc. | Chemical and pharmacological standardization of herbal extracts |
WO2001015717A1 (en) | 1999-08-30 | 2001-03-08 | Japan Science And Technology Corporation | Brain cell or nerve cell protecting agents comprising ginseng |
CA2307393A1 (en) * | 2000-05-01 | 2001-11-01 | The University Of British Columbia | Ginsenoside chemotherapy |
CN1167424C (en) | 2000-11-18 | 2004-09-22 | 唐修文 | Notoginsenoside enteric tablet |
US7011096B2 (en) * | 2001-08-31 | 2006-03-14 | Philip Morris Usa Inc. | Oxidant/catalyst nanoparticles to reduce carbon monoxide in the mainstream smoke of a cigarette |
US20030185910A1 (en) * | 2002-02-08 | 2003-10-02 | Taik Koo Yun | Cancer preventive composition comprising ginsenoside glycosides of red ginseng |
US6936283B2 (en) * | 2003-07-25 | 2005-08-30 | Langeland Bjoern T. | Composition for stimulation of specific metallo-enzymes |
US7186517B2 (en) * | 2003-08-01 | 2007-03-06 | Aesgen, Inc. | Compositions and methods for monitoring breast cancer treatment |
CN100563668C (en) * | 2003-08-18 | 2009-12-02 | 株式会社柳柳 | Use the gen-seng and the processing thereof of vinegar |
KR20050081247A (en) | 2004-02-12 | 2005-08-18 | 이처준 | Broth to chase a hangover make use of ginseng steamed red and ginseng steamed black |
US20080021083A1 (en) | 2004-03-03 | 2008-01-24 | Daley Thomas E | 4-Methylpyrazole Formulations for Inhibiting Ethanol Intolerance |
KR100547253B1 (en) | 2004-05-29 | 2006-01-26 | 박명환 | Treating and prevention of cancer with new ginsenoside derivatives |
CN1698879B (en) | 2005-06-21 | 2010-08-11 | 蔺益民 | Product having sobering up and liver protecting functions and its preparation method and usage |
JP5371428B2 (en) * | 2005-07-29 | 2013-12-18 | ティーマ ファウンデーション | Composition for reducing alcohol metabolism and reducing the risk of alcohol-induced diseases |
-
2009
- 2009-01-23 MY MYPI2010003500A patent/MY160074A/en unknown
- 2009-01-23 NZ NZ587134A patent/NZ587134A/en not_active IP Right Cessation
- 2009-01-23 KR KR1020107018644A patent/KR101648987B1/en active IP Right Grant
- 2009-01-23 ES ES09704632T patent/ES2400491T3/en active Active
- 2009-01-23 US US12/863,979 patent/US8440632B2/en not_active Expired - Fee Related
- 2009-01-23 JP JP2010544334A patent/JP5523348B2/en not_active Expired - Fee Related
- 2009-01-23 AU AU2009206753A patent/AU2009206753B2/en not_active Ceased
- 2009-01-23 DK DK09704632.0T patent/DK2254569T3/en active
- 2009-01-23 CN CN2009801101030A patent/CN101977600B/en not_active Expired - Fee Related
- 2009-01-23 CA CA2713104A patent/CA2713104C/en not_active Expired - Fee Related
- 2009-01-23 EP EP09704632A patent/EP2254569B1/en not_active Not-in-force
- 2009-01-23 KR KR1020167010378A patent/KR20160048228A/en not_active Application Discontinuation
- 2009-01-23 WO PCT/US2009/000431 patent/WO2009094177A1/en active Application Filing
- 2009-01-23 TW TW098103157A patent/TWI440463B/en not_active IP Right Cessation
-
2010
- 2010-12-02 HK HK10111249.4A patent/HK1144772A1/en not_active IP Right Cessation
Non-Patent Citations (1)
Title |
---|
See references of WO2009094177A1 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017532053A (en) * | 2014-10-28 | 2017-11-02 | ロブスト シード テクノロジー エーアンドエフ アクチエボラーグ | Improved method of seed priming |
US10645861B2 (en) | 2014-10-28 | 2020-05-12 | Robust Seed Technology A&F Aktiebolag | Method for seed priming |
CN109758464A (en) * | 2019-03-21 | 2019-05-17 | 淮阴师范学院 | Application of Vietnam ginsenoside R4 in preparation neurodegenerative disease therapeutic agent |
Also Published As
Publication number | Publication date |
---|---|
WO2009094177A1 (en) | 2009-07-30 |
AU2009206753A1 (en) | 2009-07-30 |
KR20160048228A (en) | 2016-05-03 |
KR20100111300A (en) | 2010-10-14 |
TW200936144A (en) | 2009-09-01 |
DK2254569T3 (en) | 2013-02-25 |
CN101977600A (en) | 2011-02-16 |
CN101977600B (en) | 2013-02-27 |
EP2254569B1 (en) | 2012-11-28 |
US8440632B2 (en) | 2013-05-14 |
AU2009206753B2 (en) | 2014-07-03 |
JP2011510075A (en) | 2011-03-31 |
HK1144772A1 (en) | 2011-03-11 |
NZ587134A (en) | 2012-04-27 |
US20110065659A1 (en) | 2011-03-17 |
ES2400491T3 (en) | 2013-04-10 |
KR101648987B1 (en) | 2016-08-17 |
TWI440463B (en) | 2014-06-11 |
CA2713104C (en) | 2016-07-12 |
JP5523348B2 (en) | 2014-06-18 |
CA2713104A1 (en) | 2009-07-30 |
MY160074A (en) | 2017-02-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2009206753B2 (en) | Protopanaxadiol-type ginsenoside compositions and uses thereof | |
US11241406B2 (en) | Compositions and methods for acutley raising nitric oxide levels | |
JP7473516B2 (en) | A formula that promotes gut health | |
JP2009502958A (en) | How to treat or manage stress | |
KR20080105470A (en) | Food composition containing ginseng fruit extract for preventing and improving obesity | |
MX2011007842A (en) | Treatment of neurotrophic factor mediated disorders. | |
JP4009642B2 (en) | Composition for improving obesity | |
US20200261392A1 (en) | Method of treatment | |
EP2068902A2 (en) | Tea-derived compostiions and methods of using same for cardiovascular health | |
WO2005082390A1 (en) | Fat accumulation inhibitors | |
KR20110121239A (en) | Composition comprising skin of onion for preventing or treating lipid metabolism disorder | |
JP6916422B2 (en) | Bone resorption inhibitory composition and bone resorption inhibitory food composition | |
US20230355563A1 (en) | Hunger suppression | |
EP4041269A1 (en) | Improved anti-hangover composition, its preparation and uses | |
KR20110100882A (en) | Composition comprising quercetin for preventing or treating lipid metabolism disorder | |
JP2009023948A (en) | Dopamine-inhibiting agent | |
US20170035791A1 (en) | Combination of beta-glucosylceramide and polyethoxylated castor oil and other adjuvants for controling blood sugar levels, immunoprotection and hepatoprotection |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20100818 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR |
|
AX | Request for extension of the european patent |
Extension state: AL BA RS |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1144772 Country of ref document: HK |
|
DAX | Request for extension of the european patent (deleted) | ||
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: REF Ref document number: 585774 Country of ref document: AT Kind code of ref document: T Effective date: 20121215 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 602009011516 Country of ref document: DE Effective date: 20130124 |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: T3 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: KIRKER AND CIE S.A., CH |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: TRGR |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: T3 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1144772 Country of ref document: HK |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2400491 Country of ref document: ES Kind code of ref document: T3 Effective date: 20130410 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MK05 Ref document number: 585774 Country of ref document: AT Kind code of ref document: T Effective date: 20121128 |
|
REG | Reference to a national code |
Ref country code: NO Ref legal event code: T2 Effective date: 20121128 |
|
REG | Reference to a national code |
Ref country code: LT Ref legal event code: MG4D |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20130301 Ref country code: PT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20130328 Ref country code: PL Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 Ref country code: SI Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 Ref country code: LV Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: AT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BG Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20130228 Ref country code: EE Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 Ref country code: CZ Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 Ref country code: SK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20130131 Ref country code: RO Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed |
Effective date: 20130829 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CY Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 602009011516 Country of ref document: DE Effective date: 20130829 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20130731 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R082 Ref document number: 602009011516 Country of ref document: DE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: TR Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20130123 Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO Effective date: 20090123 Ref country code: MK Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 8 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IS Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20121128 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 9 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 10 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20180126 Year of fee payment: 10 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20180127 Year of fee payment: 10 Ref country code: DK Payment date: 20180125 Year of fee payment: 10 Ref country code: DE Payment date: 20180129 Year of fee payment: 10 Ref country code: GB Payment date: 20180129 Year of fee payment: 10 Ref country code: FI Payment date: 20180129 Year of fee payment: 10 Ref country code: NO Payment date: 20180129 Year of fee payment: 10 Ref country code: ES Payment date: 20180201 Year of fee payment: 10 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IE Payment date: 20180129 Year of fee payment: 10 Ref country code: FR Payment date: 20180125 Year of fee payment: 10 Ref country code: BE Payment date: 20180129 Year of fee payment: 10 Ref country code: IT Payment date: 20180122 Year of fee payment: 10 Ref country code: SE Payment date: 20180129 Year of fee payment: 10 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R119 Ref document number: 602009011516 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: EBP Effective date: 20190131 Ref country code: NO Ref legal event code: MMEP |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: MM Effective date: 20190201 |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20190123 |
|
REG | Reference to a national code |
Ref country code: BE Ref legal event code: MM Effective date: 20190131 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: MM4A |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190124 Ref country code: FI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190123 Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190801 Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190201 Ref country code: NO Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190131 Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190131 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190131 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190131 Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190131 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190123 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190123 Ref country code: DK Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190131 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190123 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20200310 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190124 |